Jen-Hong Lan

Using Multivariate Regression Model with Least Absolute Shrinkage and Selection Operator (LASSO) to Predict the Incidence of Xerostomia after Intensity-Modulated Radiotherapy for Head and Neck Cancer

Purpose The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Methods and Materials Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3+ xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R2, chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Results Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R2 was satisfactory and corresponded well with the expected values. Conclusions Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT.

Dosimetric Comparison of Helical Tomotherapy and Dynamic Conformal Arc Therapy in Stereotactic Radiosurgery for Vestibular Schwannomas

The dosimetric results of stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) performed using dynamic conformal arc therapy (DCAT) with the Novalis system and helical TomoTherapy (HT) were compared using plan quality indices. The HT plans were created for 10 consecutive patients with VS previously treated with SRS using the Novalis system. The dosimetric indices used to compare the techniques included the conformity index (CI) and homogeneity index (HI) for the planned target volume (PTV), the comprehensive quality index (CQI) for nine organs at risk (OARs), gradient score index (GSI) for the dose drop-off outside the PTV, and plan quality index (PQI), which was verified using the plan quality discerning power (PQDP) to incorporate 3 plan indices, to evaluate the rival plans. The PTV ranged from 0.27-19.99 cm(3) (median 3.39 cm(3)), with minimum required PTV prescribed doses of 10-16 Gy (median 12 Gy). Both systems satisfied the minimum required PTV prescription doses. HT conformed better to the PTV (CI: 1.51 ± 0.23 vs. 1.94 ± 0.34; p < 0.01), but had a worse drop-off outside the PTV (GSI: 40.3 ± 10.9 vs. 64.9 ± 13.6; p < 0.01) compared with DCAT. No significant difference in PTV homogeneity was observed (HI: 1.08 ± 0.03 vs. 1.09 ± 0.02; p = 0.20). HT had a significantly lower maximum dose in 4 OARs and significant lower mean dose in 1 OAR; by contrast, DCAT had a significantly lower maximum dose in 1 OAR and significant lower mean dose in 2 OARs, with the CQI of the 9 OARs = 0.92 ± 0.45. Plan analysis using PQI (HT 0.37 ± 0.12 vs. DCAT 0.65 ± 0.08; p < 0.01), and verified using the PQDP, confirmed the dosimetric advantage of HT. However, the HT system had a longer beam-on time (33.2 ± 7.4 vs. 4.6 ± 0.9 min; p < 0.01) and consumed more monitor units (16772 ± 3803 vs. 1776 ± 356.3; p < 0.01). HT had a better dose conformity and similar dose homogeneity but worse dose gradient than DCAT. Plan analysis confirmed the dosimetric advantage of HT, although not all indices revealed a better outcome for HT. Whether this dosimetric advantage translates into a clinical benefit deserves further investigation.

A Prospective Cohort Study to Compare Treatment Results Between 2 Fractionation Schedules of High-Dose-Rate Intracavitary Brachytherapy (HDR-ICBT) in Patients With Cervical Cancer

PURPOSE To compare the treatment results of 2 fractionation schedules for high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. METHODS AND MATERIALS From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy×4 (HDR-4) (n=144) or 4.5 Gy×6 (HDR-6) (n=123) to point A of ICBT using 192Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. RESULTS There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5-year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged≥62 years old (P=.012) but not in patients aged<62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. CONCLUSION The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT.

Factors for Predicting Rectal Dose of High-Dose-Rate Intracavitary Brachytherapy After Pelvic Irradiation in Patients With Cervical Cancer: A Retrospective Study With Radiography-Based Dosimetry

PURPOSE To evaluate the predictive factors for rectal dose of the first fraction of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. METHODS AND MATERIALS From March 1993 through February 2008, 946 patients undergoing pelvic irradiation and HDR-ICBT were analyzed. Examination under anesthesia (EUA) at the first implantation of the applicator was usually performed in the early period. Rectal point was determined radiographically according to the 38th Report of the International Commission of Radiation Units and Measurements (ICRU). The ICRU rectal dose (PRD) as a percentage of point A dose was calculated; multiple linear regression models were used to predict PRD. RESULTS Factors influencing successful rectal dose calculation were EUA (p < 0.001) and absence of diabetes (p = 0.047). Age (p < 0.001), body weight (p = 0.002), diabetes (p = 0.020), and EUA (p < 0.001) were independent factors for the PRD. The predictive equation derived from the regression model was PRD (%) = 57.002 + 0.443 x age (years) - 0.257 x body weight (kg) + 6.028 x diabetes (no: 0; yes: 1) - 8.325 x EUA (no: 0; yes: 1) CONCLUSION Rectal dose at the first fraction of HDR-ICBT is positively influenced by age and diabetes, and negatively correlated with EUA and body weight. A small fraction size at point A may be considered in patients with a potentially high rectal dose to reduce the biologically effective dose if the ICRU rectal dose has not been immediately obtained in the first fraction of HDR-ICBT.

Propensity-score-matched evaluation of the incidence of radiation pneumonitis and secondary cancer risk for breast cancer patients treated with IMRT/VMAT

Propensity score matching evaluates the treatment incidence of radiation-induced pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer patients. Of 32 patients treated with IMRT and 58 who received VMAT were propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of acute and chronic toxicity, respectively. Self-fitted normal tissue complication probability (NTCP) parameter values were used to analyze the risk of RP. SCRs were evaluated using the preferred Schneider’s parameterization risk models. The dosimetric parameter of the ipsilateral lung volume receiving 40 Gy (IV40) was selected as the dominant risk factor for the RP NTCP model. The results showed that the risks of RP and NTCP, as well as that of SCR of the ipsilateral lung, were slightly lower than the values in patients treated with VMAT versus IMRT (p ≤ 0.01). However, the organ equivalent dose and excess absolute risk values in the contralateral lung and breast were slightly higher with VMAT than with IMRT (p ≤ 0.05). When compared to IMRT, VMAT is a rational radiotherapy option for breast cancer patients, based on its reduced potential for inducing secondary malignancies and RP complications.

Physical Characteristics of Fixed and Dynamics Collimator for Cyberknife M6

This research describes the estimation and quantization of physical benefit for the fixed/variable aperture collimator (Iris) of Cyberknife M6. The fixed collimator and Iris were measured of output factors in different depths (650, 800 and 1000 mm) with an ionization chamber inside a water phantom, and the physical characteristic of profile was compared in different depths (5, 7.5, 10, 12.5, 15, 20, 25, 30, 35, 40, 50 and 60 mm in diameter). The results of this study showed that the great difference of output factor for two collimators is fixed collimator higher than 25.88% with Iris in 5 mm cone size and in SAD 800 mm, and 3.4% for 7.5 mm cone size. The other output factor differences between fixed and Iris are all less than 1%. The biggest different of penumbra of fixed and Iris are in 50 and 60 mm cone sizes.

Relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis after breast hybrid intensity modulation radiation therapy

To evaluate the relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis (RD) after breast hybrid intensity modulation radiation therapy (IMRT). The study cohort consisted of 95 breast cancer patients treated with hybrid IMRT. RD grade ≥2 (2+) toxicity was defined as clinically significant. Patient characteristics and the irradiation treatment planning parameters were used as the initial candidate factors. Prognostic factors were identified using the least absolute shrinkage and selection operator (LASSO)-based normal tissue complication probability (NTCP) model. A univariate cut-off dose NTCP model was developed to find the dose-volume limitation. Fifty-two (54.7%) of ninety-five patients experienced acute RD grade 2+ toxicity. The volume of skin receiving a dose >35 Gy (V35) was the most significant dosimetric predictor associated with RD grade 2+ toxicity. The NTCP model parameters for V35Gy were TV50 = 85.7 mL and γ50 = 0.77, where TV50 was defined as the volume corresponding to a 50% incidence of complications, and γ50 was the normalized slope of the volume-response curve. Additional potential predictive patient characteristics were energy and surgery, but the results were not statistically significant. To ensure a better quality of life and compliance for breast hybrid IMRT patients, the skin volume receiving a dose >35 Gy should be limited to <85.7 mL to keep the incidence of RD grade 2+ toxicities below 50%. To avoid RD toxicity, the volume of skin receiving a dose >35 Gy should follow sparing tolerance and the inherent patient characteristics should be considered.

Radiation-induced secondary malignancies for nasopharyngeal carcinoma: a pilot study of patients treated via IMRT or VMAT

Background Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. Patients and methods We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider’s full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. Results We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. Conclusion VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.

Using Kalman Filter with Morphological Image Operation Tracking a Moving Target in Radiotherapy

Kalman filter using an operator formulation for a moving object in a sequence of images during the radiotherapy for tracking respiratory subject is presented. the algorithm of position processing with a high-accuracy position estimation technique produced real-time and fast position calculations. the position of a few pixels of the moving object because of position was measured successfully. the results suggest that quantitative assessments of the moving marker should be possible with Kalman filter.